Leishmaniasis lends itself to detailed immunological analysis and thus can serve as a model for protozoan infections. The objective of the proposal is to assess the nature of protective immunity to experimental leishmania infection in animal models. Three lines of research will be followed: 1) The mechanisms of immunity will be examined in mice of healing and non-healing inbred strains infected with L.tropica: the induction of sensitized lymphocytes will be monitored by blast transformation and thymidine uptake, and the ability of these lymphocytes to induce macrophage activation will be measured. 2) Activated infected macrophages from healing and non-healing strains will be studied by electron microscopy to examine the relationship between parasites and intracellular organelles. 3) Mice and guinea-pigs exposed to non-pathogenic leishmania species will be subsequently infected with the pathogenic organisms. The course of infection, the cross-reactions between pathogenic and non-pathogenic parasites at the humoral (by immunofluorescence) and cellular (by blast transformation and thymidine uptake) levels will be analyzed, as well as the ability of lymphocytes from sensitized animals to activate macrophages in the presence of antigens from the pathogenic and non-pathogenic organisms.